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Non\u2010obese diabetic\/LtJ mice, a well\u2010established pSS model, were used as the model group and treated with OD or hydroxychloroquine. Fecal and tissue samples were collected starting 4\u2009weeks after administration. Basic pathological examination, 16S rRNA sequencing, and ultra\u2010high\u2010performance liquid chromatography\u2013mass spectrometry were employed to assess changes in tissue function, inflammation levels, gut microbiota, and metabolite profiles across all groups. The results showed that OD reduced the expression levels of inflammatory factors, regulated immune balance, and ameliorated functional damage of the submandibular gland. It also modulated the abundance of Rikenella, Mycoplasmataceae, Mycoplasmatales, and Erysipelotrichales, thereby affecting glycerophospholipid metabolism and improving the disease phenotype in pSS mice. In conclusion, OD may treat pSS by lowering inflammation, restoring salivary gland function, and correcting gut microbiota and metabolic imbalances.<\/jats:p>","DOI":"10.1002\/bmc.70468","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T10:47:47Z","timestamp":1778582867000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ophiopogonin D Mediates Therapeutic Effects on Primary Sj\u00f6gren's Syndrome by Modulating Gut Microbiota and Metabolite Profiles"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6981-3240","authenticated-orcid":false,"given":"Fengtao","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Guang'anmen Hospital Chinese Academy of Chinese Medical Sciences  Beijing 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